Method of controlling a microfluidic device having a reduced number of input and output connections

ABSTRACT

A system and method for reducing the number of input/output connections required to connect a microfluidic substrate to an external controller for controlling the substrate. A microfluidic processing device is fabricated on a substrate having a plurality of N independently controllable components, (e.g., a resistive heating elements) each having at least two terminals. The substrate includes a plurality of input/output contacts for connecting the substrate to an external controller, and a plurality of leads for connecting the contacts to the terminals of the components. The leads are arranged to allow the external controller to supply control signals to the terminals of the components via the contacts using substantially fewer contacts than the total number of component terminals. The components are independently controlled by arranging the leads so that each component&#39;s terminals are connected to a unique combination of contacts.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/717,075, entitled “Microfluidic Devices Having a Reduced Number ofInput and Output Connections,” filed Mar. 3, 2010; which is acontinuation of U.S. patent application Ser. No. 10/489,404, entitled“Microfluidic Devices Having a Reduced Number of Input and OutputConnections,” filed Mar. 7, 2005, now U.S. Pat. No. 7,674,431, issuedMar. 9, 2010; which claims the benefit of PCT Application No.PCT/US02/29012, entitled “Microfluidic Devices Having a Reduced Numberof Input and Output Connections,” filed Sep. 12, 2002; which is acontinuation in part of U.S. patent application Ser. No. 09/949,763,entitled “Microfluidic Devices Having a Reduced Number of Input andOutput Connections,” filed Sep. 12, 2001, now U.S. Pat. No. 6,852,287,issued Feb. 8, 2005. The entire disclosure of each of theabove-referenced applications is hereby incorporated by reference in itsentirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to microfluidic devices, and moreparticularly to techniques for reducing the number of input and outputconnections required to connect a microfluidic device to an externalcontroller for controlling the microfluidic device.

2. Description of the Related Art

Micro/nano technology devices are known in the art as devices withcomponents on the scale of 1 μn to 100 s of μm that cooperate to performvarious desired functions. In particular, microfluidic devices aremicro/nano technology devices that perform fluid handling functionswhich, for example, cooperate to carry out a chemical or biochemicalreaction or analysis.

Microfluidic devices include a variety of components for manipulatingand analyzing the fluid within the devices. Typically, these elementsare microfabricated from substrates made of silicon, glass, ceramic,plastic, and/or quartz. These various fluid-processing components arelinked by microchannels, etched into the same substrate, through whichthe fluid flows under the control of a fluid propulsion mechanism.Electronic components may also be fabricated on the substrate, allowingsensors and controlling circuitry to be incorporated in the same device.Because all of the components are made using conventionalphotolithographic techniques, multi-component devices can be readilyassembled into complex, integrated systems.

Most microfluidic devices in the prior art are based on fluid flowingthrough micro-scale passages and chambers, either continuously or inrelatively large aliquots. Fluid flow is usually initiated andcontrolled by electro-osmotic and electrophoretic forces. See, e.g.,U.S. Pat. No. 5,632,876, issued Apr. 27, 1997 and entitled “Apparatusand Methods for Controlling Fluid Flow in Microchannels;” U.S. Pat. No.5,992,820, issued Nov. 30, 1999 and entitled “Flow Control inMicrofluidics Devices by Controlled Bubble Formation;” U.S. Pat. No.5,637,469, issued Jun. 10, 1997 and entitled “Methods and Apparatus forthe Detection of an Analyte Utilizing Mesoscale Flow Systems;” U.S. Pat.No. 5,800,690, issued Sep. 1, 1998 and entitled “Variable Control ofElectroosmotic and/or Electrophoretic Forces Within a Fluid-ContainingStructure Via Electrical Forces;” and U.S. Pat. No. 6,001,231, issuedDec. 14, 1999 and entitled “Methods and Systems for Monitoring andControlling Fluid Flow Rates in Microfluidic Systems.” See also productsfrom, e.g., Orchid, Inc. (www.orchid.com) and Caliper Technologies, Inc.(www.calipertech.com).

Microfluidic devices that manipulate very small aliquots of fluids (knowherein as “micro-droplets”) in micro-scale passages rely principally onpressure and other non-electric forces to move the liquid volume. Thesedevices are advantageous because smaller volumes of reagents arerequired and because non-electric propulsion forces can be generatedusing relatively small voltages, on the same order of magnitude asvoltages required by standard microelectronic components. See, i.e. thefollowing patents, the contents of which are incorporated herein intheir entirety by reference: U.S. Pat. No. 6,057,149, issued May 2, 2000and entitled “Microscale Devices And Reactions In Microscale Devices;”U.S. Pat. No. 6,048,734, issued Apr. 11, 2000 and entitled “ThermalMicrovalves in a Fluid Flow Method;” and U.S. Pat. No. 6,130,098, issuedOct. 10, 2000. (Citation or identification of any reference in thissection or any section of this application shall not be construed thatsuch reference is available as prior art to the present invention).

U.S. Pat. No. 6,130,098 (“the '098 patent”), for example, disclosesmicrofluidic devices that include micro-droplet channels fortransporting fluid droplets through a fluid processing system. Thesystem includes a variety of micro-scale components for processing thefluid droplets, including micro-reaction chambers, electrophoresismodules, and detectors (such as radiation detectors). In someembodiments, the devices also include air chambers coupled to resistiveheaters to internally generate air pressure to automatically withdraw ameasured volume of fluid from an input port, and to propel the measuredmicro-droplet through the microfluidic device.

These components are connected to input/output (I/O) pins at the edge ofthe micro-fluid device which mate with corresponding I/O pins of theexternal controller. The external controller operates these componentsby sending and receiving control signals via the input/output pins. Forexample, a control device, external to the microfluidic device,activates a resistive heater within a microfluidic device by supplyingcurrent to the heater through the input/output pins. Microfluidicdevices can include a large number of such components which arecontrolled by external devices. Accordingly, an object of the presentinvention is to reduce the number of input/output pins required forcontrolling such microfluidic devices from such external controllers.

SUMMARY OF THE INVENTION

The invention relates generally to techniques for reducing the number ofinput/output connections required to connect a microfluidic substrate toan external controller for controlling the substrate. In one aspect, theinvention involves a microfluidic processing device fabricated on asubstrate having a plurality of N independently controllable components,(e.g., resistive heating elements) each having at least two terminals.The substrate includes a plurality of input/output contacts forconnecting the substrate to an external controller, and a plurality ofleads for connecting the contacts to the terminals of the components.

The leads are arranged to allow the external controller to supplycontrol signals to the terminals of the components via the contactsusing substantially fewer contacts than the total number of componentterminals. For example, in one embodiment, each lead connects acorresponding contact to a plurality of terminals to allow thecontroller to supply to signals to the terminals without requiring aseparate contact for each terminal. The number of contacts may be lessthan about 50% of the number of components. However, to assure that thecomponents can each be controlled independently of the others, the leadsare also arranged so that each component's terminals are connected to aunique combination of contacts. Thus, the external controller canactivate a selected component by supplying control signals to thecombination of contacts uniquely associated with that component.

The substrate of the microfabricated device preferably includes elementssuch as valves or pumps, which cooperate to manipulate fluid withinchannels and chambers of the substrate. For example, the substrate mayinclude a thermally actuated valve. At least one of the N independentlycontrollable components is a heating element in thermal communicationwith the thermally actuated valve. Actuation of the heating elementactuates the valve, whereupon the valve opens or closes. The substratemay include a plurality of thermally actuated valves and a plurality ofthe N independently controllable components are heating elements inthermal communication with respective thermally actuated valves.

The substrate may include a thermally actuated pump comprising a volumeof fluid. At least one of the N independently controllable components isa heating element in thermal communication with the volume of fluid,whereby actuation of the heating element heats the fluid and actuatesthe thermally actuated pump. For example, the fluid may be a gas,whereby expansion of the gas propels a microfluidic sample along achannel of the substrate. The substrate may include a plurality ofthermally actuated pumps. Fluid of each pump is in thermal communicationwith at least one heating element.

The substrate may include at least one microfabricated reaction chamber,such as a chamber configured to perform a polymerase chain reaction. Atleast one of the N independently controllable components is a heatingelement in thermal communication with the reaction chamber, wherebyactuation of the heating element may raise a temperature of materialpresent in the reaction chamber. At least one of the N independentlycontrollable components may be a heat sensor in thermal communicationwith the reaction chamber, whereby the temperature of the materialpresent in the reaction chamber may be determined.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention may be understood more fully by reference to thefollowing detailed description of the preferred embodiment of thepresent invention, illustrative examples of specific embodiments of theinvention, and the appended figures wherein:

FIG. 1 illustrates a microfluidic control system having a discretedroplet microfluidic processing device, an external controller, and ageneral purpose computer;

FIG. 2 illustrates the discrete droplet microfluidic processing deviceof FIG. 1;

FIG. 3 illustrates the external controller of FIG. 1;

FIGS. 4A-B illustrate a micro-valve actuator;

FIG. 5 illustrates a heating component having resistive temperaturedetectors;

FIGS. 6A-B illustrate a micro-valve actuator having a reduced number ofI/O contacts;

FIGS. 7A-B illustrate a technique for sharing conductive leads thatsupply current to resistive heaters within a microfluidic processingdevice;

FIGS. 8A-B illustrate a technique for sharing conductive leads forresistive temperature detectors (“RTDs”);

FIGS. 9A-B illustrate a technique for sharing conductive leads forresistive heaters and RTDs.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

System Overview

FIG. 1 depicts a microfluidic processing system that includes amicrofluidic substrate 10, a chip carrier cartridge 20, a dataacquisition and control board (“DAQ”) 26, and a portable computer 27such as a laptop or palmtop computer. Microfluidic substrate 10 hasmicrochannels and fluid control elements formed in a solid substratesuch as silicon, glass, or other suitable material, preferablymicrofabricated using conventional photolithographic techniques. Themicrofluidic substrate 10 is mounted on the chip carrier cartridge 20.The microfluidic substrate 10 has electrical and optical connections 12with the chip carrier cartridge for carrying electrical and opticalsignals between the microfluidic substrate and the chip carrier. Forexample, the electrical connections can be formed with well-known wirebonding techniques. Furthermore, the chip carrier cartridge 20 haselectrical and optical contacts 21 for carrying electrical and opticalsignals between the microfluidic substrate and the data acquisitionboard 26.

The chip carrier cartridge 20 is shown being inserted into (or removedfrom) an interface hardware receptacle of DAQ 26 having electrical andoptical contacts 25 standardized to mate with a corresponding contacts21 of the chip carrier cartridge. Most contacts are for electricalsignals, while certain are for optical signals (IR, visible, UV, etc.)in the case of optically-monitored or optically-excited microfluidicprocessors. Alternatively (not shown), the entire data acquisition andcontrol board 26 may be a single ASIC chip that is incorporated into thechip carrier cartridge 20, wherein contacts 21, 25 would become lines ona printed circuit board.

In general, DAQ 26 controls the operation of microfluidic substrate 10via contacts 12, 21, 25 using electrical and optical signals. Portablecomputer 27 typically performs high level functions, such as supplying auser interface that allows the user to select desired operations and toview the results of such operations. As shown in FIG. 1, the computer 27is connected to DAQ 26 via connection 28, which provides data I/O,power, ground, reset, and other function connectivity. Computer 27 canalso, as shown, be used to control a laboratory robot 24 via link 31.Alternatively, a wireless link 32 between the computer 27 and the DAQ 26may be provided for data and control signal exchange via wirelesselements 32(a) and 32(b). Where the data link is a wireless link, forexample, the DAQ 26 may have separate power source such as, for example,a battery.

The present invention is directed to techniques for reducing the numberof contacts 12, 21, 25 required for communication between themicrofluidic substrate 10, chip carrier cartridge 20, and the externalcontroller or controllers such as DAQ 26.

As explained below, the number of such contacts can become extremelylarge for microfluidic substrates that include many components which areindependently controlled by an external controller. The followingdescription of the operation of a microfluidic substrate 10 and DAQ 26demonstrates the relationship between the complexity of the microfluidicsubstrate and the requisite number of contacts 12, 21, 25.

Structure of Microfluidic Processor

In the example shown in FIG. 1, a microfluidic substrate 10 includesthree inlet ports 22 for accepting fluid reagents or samples.Preferably, these inlet ports are in a standard position on thesubstrate so that laboratory robot 24, where available, may be easilyprogrammed for automatic loading of ports of several types ofmicrofluidic processors. Otherwise, the ports should be accessible formanual loading. Where possible, reagents may also be pre-packaged on themicrofluidic substrate and/or the chip carrier 20. Additionally, chipcarrier 20 has micro-circuit 23 accessible through standard connectorsfor storing, for example, self-descriptive processor information.Alternately, chip carrier cartridge 20 may bear indicia such as a barcode to indicate the device type or further information.

FIG. 2 illustrates, schematically and not to scale, the generalstructure of an exemplary integrated microfluidic substrate. Thismicrofluidic substrate is constructed from three types ofsub-assemblies. In particular, this substrate has four separatesub-assemblies: two micro-droplet metering sub-assemblies, metering 1and metering 2; one mixing sub-assembly, mixing 1; and onereaction/detection sub-assembly, reaction/detection.

These sub-assemblies are constructed from a variety of components oractuators as shown. The components include heater actuators, valveactuators, and an optical detector, all interconnected with passiveinlets, overflows, vents, and reservoirs. More specifically,sub-assembly metering 1 includes inlet 1, overflow 1, valve 1, heater,and passage 1. Similarly, sub-assembly metering 2 includes inlet 2,overflow 2, valve 2, heater 2, and passage 2. The mixing subassembly,mixing 1, includes heater, heater 2, valve 3, valve 4, vent 1, vent 2,Y-shaped passage 3, and passage 4. Finally, reaction/detection 1sub-assembly includes valve 5, valve 6, heater 3, and passage 5.

Operations of the sub-assemblies result from the coordinated operationsof their component actuators under the control of an externalcontroller, DAQ 26. The specific operation of microfluidic substrate 10is described in greater detail in co-pending application Ser. No.09/819,105, which is incorporated herein by reference. However, thefollowing describes the general operation of the fluid processor underthe control of DAQ 26.

First, fluid is introduced into inlet 1, for example, by an externalrobotic device, and flows up to the stable position created by the firsthydrophobic region h3 just beyond the widening of passage 1. Any excessfluid flows out through port overflow 1. Next, DAQ 26 instructssub-assembly metering 1 to measure a micro-droplet of determined volumefrom an aliquot of fluid introduced through port inlet 1, as describedin co-pending application Ser. No. 09/819,105. Sub-assembly metering 2is constructed and operates similarly to extract a measuredmicro-droplet of fluid from a second fluid sample likewise supplied atinlet 2.

After the pair of microdroplets are extracted from the inlet ports, DAQ26 supplies current to heater 1 and heater 2 to generate gas pressure topropel the two microdroplets through Y-shaped passage 3 and alongpassage 4 to the stable position in passage 5 just beyond the junctionof the side passage to vent 2. During this step, the two microdropletsmerge and mix to form a single, larger micro-droplet.

Next, DAQ 26 supplies current to valve 5 and valve 6 to close thesevalves and isolate the micro-droplet along passage 5. DAQ 26 directs thesub-assembly reaction/detection 1 to stimulate a reaction in the trappedmicro-droplet by, for example, supplying current to heater 3, whichheats the micro-droplet. The DAQ then monitors the results of thestimulated reaction by optically detecting radiation conducted byoptical paths o1 and o2. DAQ 26 performs these control functions byselectively supplying electrical (and sometimes optical) signals to themicrofluidic substrate via contacts 12, 21, 25.

DAQ Board Architecture

FIG. 3 illustrates a preferred hardware architecture for DAQ board 26.The DAQ board has one or more receptacles, slots, or sockets, where oneor more replaceable microfluidic processors may be accommodated in afirmly supporting manner with good contact to its external contacts.

As shown, electrical contacts 25(a) on the DAQ mate with correspondingcontacts 21(a) of the chip carrier cartridge 20. Thus, leads 39, 40 ofthe DAQ are electrically connected to corresponding leads of the chipcarrier cartridge 20. Similarly, contacts 25(b) of the DAQ mate withcontacts 21(b) of the chip carrier cartridge, thereby connecting vialight pipe, line of sight, or by other suitable means, the DAQ's opticalcouplings 41, 42 to corresponding optical couplings on the chip carriercartridge. The electrical and optical leads of the chip carriercartridge are, in turn, connected to the microfluidic substrate 10 viacontacts 12. Thus, DAQ 26 can send and receive electrical and opticalsignals via contacts 12, 21, 25 to and from microfluidic substrate 10 inorder to engage and control a variety of components or actuators locatedthereon.

The electrical contacts, which may have many embodiments, areillustrated here as edge contacts that are engaged when the chip carriercartridge and microfluidic substrate are inserted in a DAQ boardreceptacle. Alternatively, contacts may be suitable for engaging aflexible ribbon cable, or may by multi-pin sockets, for example. Theoptical contacts may be of types known for connecting fiber-opticcables.

The DAQ includes one or more heater drivers 47 for supplying a specifiedamount of current. The output of each heater driver 47 is connected toan analog multiplexor 48 that routes the current from the driver to aselected I/O contact 25(a). For sensing functions, the DAQ includes oneor more temperature sensor drivers 49 which are each connected to ananalog multiplexor 50 that multiplexes each temperature sensor driver 49to a selected one of the plurality of I/O contacts 25(a). The DAQ alsoincludes one or more photodiodes 51 for optical detection. Multiplexor52 multiplexes these optical detectors to an analog-to digital converter(“ADC”) 55 via a selected one of the plurality of I/O contacts 25(b).Finally, the DAQ is shown including one or more laser diodes 53. Laserenable register 54 enables selected laser diode drivers, therebyemitting light signals on corresponding optical couplings 42 and opticalcontacts 25(b).

Also shown in FIG. 3, the DAQ also includes a microprocessor and memory43 for controlling the operation of the heater drivers 47, temperaturesensor drivers 49, photodiodes 51, laser diodes 53 and their associatedanalog multiplexors 48, 50, 52, as well as laser enable register 54.More specifically, the microprocessor sends control signals to thesedevices via a bus driver 45 and bus 46, and reads status informationfrom the sensing elements via the same driver 45 and bus 46. Finally,host interface 44 allows the microprocessor 43 to communicate with thegeneral purpose computer 27 (FIG. 1) via leads 38(c) or, as describedabove, via wireless means.

The operation of the DAQ is exemplified by the following description ofthe control of a simple resistive heater, such as the resistive heatershown in valve 1 of the microfluidic device depicted in FIG. 2. As shownin FIG. 2, valve 1 includes a resistive heating element 9 that isconnected at its terminals 11, 13 to a pair of I/O contacts 12(a) vialeads 8. The DAQ activates this resistive heating element by instructinganalog multiplexor 48 to connect the output of heater driver 47 to apair of I/O contacts 25(a) that are connected to corresponding I/Ocontacts 21(a) of the chip carrier cartridge 20, that are connected tocorresponding contacts 12(a) of the substrate. It then instructs heaterdriver 47 to supply a selected amount of current. The current suppliedby heater driver 47 flows through analog multiplexor 48 and to theresistive heating element 9 via the selected leads 39 and 8.

The Relationship Between the Number of I/O Pins and the Number ofControl Elements on the Microfluidic Processor

For a two terminal device, such as the resistive heater described above,the system must use two I/O contacts to supply the control signals foroperation of the device. Thus, if the number of two-terminal devices onthe microfluidic process is N, then 2×N I/O contacts are sufficient toallow DAQ 26 to independently control each of the devices.

However, for complex microfluidic devices the number of I/O contacts canbe unreasonably large. In the simple microfluidic device shown in FIG.2, where only nine different resistive heating elements are shown, onlyeighteen contacts are required. For increasingly complex microfluidicdevices having hundreds of independently controlled components, thenumber of contacts becomes excessive.

Moreover, for discrete droplet fluid processing systems such asdescribed in co-pending application Ser. No. 09/819,105, even relativelysimple microfluidic processors may employ a large number of contacts.For example, FIGS. 4A and 4B depict a preferred valve structure for suchfluid processing systems that includes three separate resistive heatersfor each valve. Referring to FIGS. 4A and 4B, the operation of thepreferred valve structure is described in detail below.

FIG. 4A depicts the valve in its open position, having a wax plug 76positioned within side channel 77. To close this valve, DAQ controllersupplies current to resistive heater HTR2 via I/O contacts 80, 81. Thiscauses HTR2 to warm, thereby melting plug 76. DAQ 26 then suppliescurrent to HTR1 via I/O contacts 82, 84 to thereby heat gas withinchamber 75. As the gas expands, it forces plug 76 to move into channel78 as shown in FIG. 4B. DAQ 26 then shuts off heater HTR2 and allows theplug to cool, thereby blocking channel 78 and side channel 77. When theplug is cool, DAQ 26 then shuts off HTR1. As HTR1 cools, the pressure inchamber 75 drops, thereby creating a negative pressure which, as will beexplained below, may be used to re-open the valve.

To open the valve, DAQ 26 supplies current to HTR3 via I/O pins 86, 88to warm the heater and thereby melt the plug. Once the plug is melted,the negative pressure in chamber 75 draws the plug back into sidechannel 77, thereby re-opening channel 78.

If such bidirectional valves are used to implement the microfluidicdevice shown in FIG. 2, the number of independently controlled resistiveelements nearly triples from nine to twenty-one. However, to accuratelycontrol the temperature of each of these resistive elements, even morecomponents may be used.

FIG. 5 depicts a six-terminal resistive heating device. The deviceincludes a two terminal heating element R1 that operates in accordancewith heating element 9 of FIG. 2. The device also includes a currentflow directional element 70, which allows current to flow substantiallyonly in a single direction between leads 55, 56. As shown in FIG. 5,current flow directional element 70 is a diode configured to allowcurrent to flow from lead 56 to lead 55. Current flow directionalelement 70 substantially prevents, and preferably excludes, current flowfrom lead 55 to lead 56. Current flow directional element 70 may be anyelement that allows current to flow predominately in one directionbetween points of a circuit. Diodes are preferred current flowdirectional elements.

The device of FIG. 5 also includes a four terminal resistive sensorelement R2 in close proximity to R1 so as to be in thermal communicationtherewith. A current flow directional element 71, which has generallythe same functional characteristics as current flow directional element70, allows current to flow in substantially one direction between leads57, 58 and leads 59, 60. In the configuration shown, current flowdirectional element 71 allows current to flow from leads 59, 60 to leads57, 58 but substantially prevents, and preferably excludes, current flowfrom leads 57, 58 to leads 59, 60.

Current flow directional elements 70 and 71 may be but are notnecessarily formed by microfabrication on a substrate with elements R1and R2. Rather, current flow directional elements 70 and 71 may bedisposed at other positions along current pathways that respectivelyinclude R1 and R2. Current flow directional elements 70 and 71 arepreferably disposed in series with R1 and R2.

The sensor R2 may operate as follows. While DAQ 26 supplies current toR1 (via leads 55, 56) it also supplies a relatively low current to R2via leads 57, 60. R2 is a resistive element whose resistance increaseswith temperature. Accordingly, the voltage across R2 increases with thetemperature in the nearby region being heated by heating element R1, andtherefore element R2 can be used to measure the temperature in thisregion. DAQ 26 determines the temperature by measuring the voltageacross R2 via leads 58, 59. More specifically, referring now to FIG. 3,DAQ 26 instructs the analog multiplexor to connect temperature sensordriver 49 to the contact pins 25(a) which are connected to leads 58, 59.Temperature sensor driver 49 then determines the voltage across R2,thereby providing a measure of the temperature in the vicinity of R1.

Thus, if such devices are used in a microfluidic processor, the numberof I/O contacts increases even further. For example, one hundred andtwenty six contacts are required for the micro-fluid processor shown inFIG. 2.

The present invention is directed to techniques for reducing the numberof I/O contacts required for an external controller, such as DAQ 26, toindependently control a large number of components within microfluidicdevices, such as those described above.

FIGS. 6A, 6B illustrate a technique for reducing the number of I/Ocontacts by structuring the leads of the microfluidic device so thateach lead serves more than one component, while still allowing DAQ 26 tocontrol each component of the microfluidic device independently of theothers. Specifically, FIGS. 6A, 6B depicts a technique for sharing I/Ocontacts among three of the two-terminal resistors of a bidirectionalvalue structure, such as shown in FIGS. 4A-B discussed above. The valveoperates essentially the same as the valve shown in FIGS. 4A, B, exceptthat it uses only four contacts rather than six. In this example, eachresistor is connected to a pair of I/O contacts and therefore can becontrolled by the DAQ in the same way as described above. Although theother resistors share these I/O contacts, no resistor shares the samepair of contacts with another. Accordingly, the DAQ is able to supplycurrent to any given resistor via the pair of associated contacts,without activating any other resistor.

More generally, the number of I/O contacts required for the independentcontrol of a plurality of resistive heaters may be reduced by arrangingthe contact wiring to each resistor in the form of a logical array. Theresulting compression of the number of I/O contacts advantageouslysimplifies communication with the entire processor. Because eachresistor requires two leads to complete an electrical circuit, accordingto a conventional arrangement of leads and contacts, a device having Nresistors requires 2N leads and 2N contacts. By configuring the contactwiring in a shared array, however, the number of required contacts canbe reduced to as few as 2/N. For example, in a device comprising 100resistors, the number of external contacts can be reduced from 200 to20.

FIGS. 7A, 7B depict a DAQ 26 directly connected to a microfluidicsubstrate 10, without the use of an intermediate chip carrier cartridge20, and show an array of resistive heaters within microfluidic substrate10. The leads between contacts 12(a) and resistive heaters 100, 102-109are shown arranged in columns and rows. However, the actual physicallayout of the leads will not necessarily be a physical array. Rather,the leads will be directly routed from the resistive components tocontacts 12(a) in any manner that allows each lead to connect to aplurality of resistors while remaining electrically isolated from otherleads.

According to this arrangement, electrical contacts for N resistors areassigned to R rows and C columns such that the product RC≧N, preferablywhere R is approximately equal to C, and most preferably where R=C. Withthis arrangement, resistors assigned to the same row share a commonelectrical lead and I/O contact 12(a). Similarly, resistors assigned tothe same column also share a lead and I/O contact 12(a). However, eachresistor has a unique address, corresponding to a unique pair of I/Ocontacts, (i.e., to its unique row/column combination in the array).Therefore, each resistor is individually actuatable by supplyingelectric current to the appropriate pair of I/O contacts.

As used herein, a “resistor” or “component” that is uniquely associatedwith a pair of contacts may also refer to a resistive network (having aplurality of resistive sub-components connected in series and/orparallel) or a component network (having a plurality of sub-componentsconnected in series or parallel). In such embodiments, allsub-components are activated together when the external controllersupplies signals across the pair of contacts uniquely associated withthose sub-components.

As shown in FIG. 7A, the leads are arranged in three rows (R_(j), wherej=1-3) and three columns (C_(i), where i=1-3). For each resistor, oneterminal is connected to a row and the other terminal is connected to acolumn. Although each resistor shares these leads with other resistors,no two resistors share the same pair of leads. In other words, eachresistor is uniquely associated with a particular row/column pair R_(j),C_(i).

FIGS. 7A, 7B illustrate the operation of this structure. Heater driver47 supplies an output voltage of twenty volts on its terminals forsupplying current to resistive heating elements 100, 102-109. Thepositive output terminal 90 is connected to a first analog multiplexor48(a). As shown, this terminal can be connected to any one of the rowsof the array of leads by individual switching elements within analogmultiplexor 48(a). Similarly, the negative output terminal 92 of heaterdriver 47 is connected to a second analog multiplexor 48(b). Multiplexer48(b) allows terminal 92 to connect to any column in the array of leads.

In FIG. 7A, the switching elements within analog multiplexors 48(a,b)are all open. Accordingly, none of the heating elements 100-109 as shownare active. FIG. 7B depicts the condition of analog multiplexors 48(a,b)after DAQ 26 has instructed them to close certain internal switches tothereby supply current to a selected one of the resistors in the array.In this example, the row switch element 50 is closed, to thereby connectthe positive terminal of heater 47 to the top row of the lead array. Thecolumn switch element 52 is also closed to connect the negative terminalof heater 47 to the middle column of the lead array. Thus, the positiveterminal 90 of heater 47 is connected to resistors 100, 102, 103 and thenegative terminal is connected to resistors 102, 105, 108. However, onlyone of these resistors, 102, is connected across both terminals ofheater 47. Accordingly only resistor 102 receives current and is heated.

Resistive heating elements 100, 102-109 are disposed in series withrespective current flow directional elements 215-223, which allowcurrent to flow in one direction between the positive output terminal 90of a heater driver 47 and a negative or ground terminal 92 of heaterdriver 47 along a current path that includes one of resistive heatingelements 100, 102-109. Current flow directional elements 215-223 arepreferably configured allow current to flow only from positive outputterminal 90 to negative output terminal 92. Thus, for example, currentmay flow from a point 224 to a point 225, through resistive heater 102to point 226 and then to point 227. The current flow directionalelements, however, prevent current from passing through current pathwaysincluding resistive heaters other than resistive heater 102. Forexample, current flow directional element 219 prevents current flowbetween points 228 and 229. Current flow directional elements 215-223may be diodes as discussed above for current flow directional elements70, 71.

FIGS. 8A, 8B, 9A, 9B depict similar arrays for the resistive elementsused to sense temperature, such as R2 shown in FIG. 5. FIG. 8A depictsone array of leads for supplying current to resistive sensors 110-118.FIG. 8B depicts another set of leads for measuring the voltage acrossthe same resistors. With this structure, the leads that are used tostimulate the resistive sensors carry no current from the heater driver47 because they are electrically isolated from heater driver 47.Similarly, the leads for sensing the voltage of the resistive sensors110-118 (FIG. 8B) carry essentially no current because they are isolatedfrom the leads that supply current from heater driver 47 and RTD driver49(a) (shown in FIGS. 7A, 7B and 8A). This structure provides the mostaccurate temperature measurement.

FIGS. 9A, 9B depict an alternative structure. As with the structureshown in FIGS. 8A, 8B, the leads for sensing the voltage acrossresistive sensors, 110-118, are isolated from both of the currentsources (heater driver 47 and RTD driver 49(a)). However, both currentsources 47, 49(a) share the same leads for current return, i.e., theleads depicted as columns in the array. This provides greatercompression of the number of leads; however, the resistivity in theshared return leads may reduce the accuracy of the temperaturemeasurement.

The arrays of FIGS. 8A, 8B, 9A, and 9B include current flow directionalelements 215′-223′, which allow current to flow in only one directionthrough resistive sensors 110-118. Thus, current flow directionalelements 215′-223′ preferably allow current to flow in only onedirection between the positive terminal of RTD driver 49(a) or RTDsensor 49(b) and the negative or ground terminal of RTD driver 49(a) orRTD sensor 49(b) along a current path that includes one of resistivesensors 110-118. Preferably, current flow directional elements 215′-223′allow current to flow from the positive terminal to the negativeterminal or ground terminal of either RTD driver or RTD sensor but notfrom the negative or ground terminal to the positive terminal thereofCurrent flow directional elements 215′-223′ may be diodes similar tocurrent flow directional elements 70, 71.

While the invention has been illustratively described herein withreference to specific aspects, features and embodiments, it will beappreciated that the utility and scope of the invention is not thuslimited and that the invention may readily embrace other and differingvariations, modifications and other embodiments. For example, the sametechniques for reducing the number of leads may be-applied to othertypes of components, not just resistors. The invention therefore isintended to be broadly interpreted and construed, as comprehending allsuch variations, modifications and alternative embodiments, within thespirit and scope of the ensuing claims.

A number of references are cited herein, the entire disclosures of whichare incorporated herein, in their entirety, by reference for allpurposes. Further, none of these references, regardless of howcharacterized above, is admitted as prior to the invention of thesubject matter claimed herein.

1. A method of controlling a microfluidic device comprising a pluralityof N independently controllable components each having at least a firstterminal and a second terminal with an external controller, the methodcomprising: sending a first current to a first independentlycontrollable component through a first lead connecting to a plurality offirst terminals of a first group of the independently controllablecomponents; receiving a first current from the first independentlycontrollable component through a second lead connecting to a pluralityof second terminals of a second group of independently controllablecomponents, wherein the first current corresponds to heating of thereaction chamber; sending a second current to a second independentlycontrollable component through a third lead connecting a plurality offirst terminals of a third group of independently controllablecomponents; and, receiving a second current from the secondindependently controllable component through a fourth lead connecting toa plurality of second terminals of a fourth group of independentlycontrollable components.
 2. The method of claim 1, wherein the secondcurrent corresponds to optical monitoring of the reaction chamber. 3.The method of claim 1, wherein the second current corresponds to heatingof a thermally operative component.
 4. The method of claim 1, whereinthe second current corresponds to moving a microdroplet in themicrofluidic device.
 5. The method of claim 1, wherein the firstindependently controllable component is the only independentlycontrollable component common to the first group and second group ofindependently controllable components.
 6. The method of claim 1, whereinthe second independently controllable component is the onlyindependently controllable component common to the third group andfourth group of independently controllable components.
 7. The method ofclaim 1, wherein the first independently controllable componentcomprises a resistive heating element.
 8. The method of claim 1, whereinthe first independently controllable component comprises a resistivesensing element.
 9. The method of claim 1, wherein one of theindependently controllable components comprises a plurality ofindependently controllable subcomponents.
 10. The method of claim 1,wherein the independently controllable subcomponents each comprise afirst and second terminal each connected to a lead.
 11. The method ofclaim 1, further comprising controlling a first subcomponent, thecontrolling comprising: sending a first subcomponent current to thefirst subcomponent through the lead connected to the first terminal ofthe first subcomponent; and, receiving a first subcomponent current fromthe first subcomponent through the lead connected to the second terminalof the first subcomponent.
 12. The method of claim 11, wherein the leadconnected to the first terminal of the first subcomponent connects to aterminal of at least one additional component or subcomponent.
 13. Themethod of claim 12, wherein the lead connected to the second terminal ofthe first subcomponent connects to a terminal of at least one additionalcomponent or subcomponent.
 14. The method of claim 13, wherein the leadconnected to the first terminal of the first subcomponent and the leadconnected to the second terminal of the first subcomponent only bothconnect the first subcomponent.
 15. The method of claim 1, wherein atleast one of the leads comprises a current directional flow element. 16.The method of claim 15, wherein the current directional flow elementcomprises a diode.
 17. The method of claim 1, further comprisingperiodically and intermittently sending the first current to cyclicallyheat the reaction chamber.
 18. A system configured to perform operationson a microdroplet, the system comprising: a microfluidic devicecomprising: a plurality of N independently controllable components eachincluding a first terminal and a second terminal; a plurality of leads,wherein each lead connects to two or more terminals which are eachassociated with a unique independently controllable component; and, areaction chamber; and, a controller comprising stored instructions tocontrol the operation of the independently controllable components,wherein the stored instruction comprise sending a current to a firstindependently controllable component corresponding to heating thereaction chamber.
 19. The system of claim 18, wherein the microfluidicdevice further comprises a current directional flow unit.
 20. The systemof claim 19, wherein the current directional flow unit comprises adiode.